Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells.

Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells.
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在大自然中寻找抗癌活性:绿大麦对白血病/淋巴瘤细胞引起的抗增殖和促凋亡作用。

DOI:
10.1371/journal.pone.0073508
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Varela-Ramirez A
Varela-Ramirez A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Robles-Escajeda E;Lerma D;Nyakeriga AM;Ross JA;Kirken RA;Aguilera RJ;Varela-Ramirez A

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通过检测绿色大麦提取物(GB)对人白血病/淋巴瘤细胞系的抗增殖和促凋亡特性来研究其可能的抗癌活性。我们的研究结果表明,GB表现出选择性的抗增殖活性的一组白血病/淋巴瘤细胞相比,非癌细胞。具体而言,GB破坏BJAB细胞内的细胞周期进程,表现为G2/M期阻滞和DNA片段化,并诱导细胞凋亡,表现为磷脂酰丝氨酸(PS)易位到外细胞质膜在两个B系白血病/淋巴瘤细胞系。GB的促凋亡作用被认为是独立的线粒体去极化,从而牵连外部细胞死亡途径发挥其细胞毒性。事实上,GB引起前B急性淋巴细胞白血病Nalm-6细胞中TNF-α产生、caspase-8和caspase-3活化以及PARP-1裂解的增加。此外,通过加入特异性半胱天冬酶抑制剂Z-VAD-FMK和Ac-DEVD-CHO,强烈抑制/阻断半胱天冬酶-8和半胱天冬酶-3活化以及PARP-1裂解。此外,细胞内信号分析确定GB处理增强Nalm-6细胞中Lck和Src酪氨酸激酶的组成性激活。综上所述,这些发现表明GB在B系白血病/淋巴瘤细胞内诱导优先的抗增殖和促凋亡信号,如通过以下细胞凋亡的生化标志所确定的:PS外化,TNF-α释放增强,caspase-8和caspase-3活化,PARP-1切割和DNA片段化我们的观察表明GB具有抗白血病/白血病的潜力。因此,需要在体内进行进一步的评价以支持这些发现。
Green barley extract (GB) was investigated for possible anti-cancer activity by examining its anti-proliferative and pro-apoptotic properties on human leukemia/lymphoma cell lines. Our results indicate that GB exhibits selective anti-proliferative activity on a panel of leukemia/lymphoma cells in comparison to non-cancerous cells. Specifically, GB disrupted the cell-cycle progression within BJAB cells, as manifested by G2/M phase arrest and DNA fragmentation, and induced apoptosis, as evidenced by phosphatidylserine (PS) translocation to the outer cytoplasmic membrane in two B-lineage leukemia/lymphoma cell lines. The pro-apoptotic effect of GB was found to be independent of mitochondrial depolarization, thus implicating extrinsic cell death pathways to exert its cytotoxicity. Indeed, GB elicited an increase of TNF-α production, caspase-8 and caspase-3 activation, and PARP-1 cleavage within pre-B acute lymphoblastic leukemia Nalm-6 cells. Moreover, caspase-8 and caspase-3 activation and PARP-1 cleavage were strongly inhibited/blocked by the addition of the specific caspase inhibitors Z-VAD-FMK and Ac-DEVD-CHO. Furthermore, intracellular signaling analyses determined that GB treatment enhanced constitutive activation of Lck and Src tyrosine kinases in Nalm-6 cells. Taken together, these findings indicate that GB induced preferential anti-proliferative and pro-apoptotic signals within B-lineage leukemia/lymphoma cells, as determined by the following biochemical hallmarks of apoptosis: PS externalization, enhanced release of TNF-α, caspase-8 and caspase-3 activation, PARP-1 cleavage and DNA fragmentation Our observations reveal that GB has potential as an anti-leukemia/lymphoma agent alone or in combination with standard cancer therapies and thus warrants further evaluation in vivo to support these findings.
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发表时间: 2010-05-18
期刊: BMC cancer
影响因子: 3.8
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DOI: 10.1182/blood-2004-10-3819
发表时间: 2005-08-15
期刊: BLOOD
影响因子: 20.3
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DOI: 10.1038/sj.onc.1202878
发表时间: 1999-09-02
期刊: ONCOGENE
影响因子: 8
作者:
Belka, C;Marini, P;Bamberg, M
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DOI: 10.1038/sj.leu.2403139
发表时间: 2003-12-01
期刊: LEUKEMIA
影响因子: 11.4
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